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Augmented expression of cytokines in mouse epidermal tumor cells and its possible involvement in the induction of hematopoietic alterations
Author(s) -
Bauluz Cristina,
Larcher Fernando,
Ballestin Claudio,
Grande Teresa,
Jorcano José L.
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110306
Subject(s) - biology , progenitor cell , haematopoiesis , cytokine , granulocyte , keratinocyte , tumor necrosis factor alpha , colony stimulating factor , granulocyte macrophage colony stimulating factor , bone marrow , cell culture , cancer research , interleukin 3 , carcinogenesis , immunology , stem cell , microbiology and biotechnology , cancer , t cell , genetics , immune system , antigen presenting cell
Mice with skin tumors induced either by 7,12‐dimethylbenz[a]anthracene complete carcinogenesis or subcutaneous injection of a carcinogenic keratinocyte cell line showed moderate to severe splenomegaly as a result of an increase in splenic granulocyte‐macrophage and erythroid (erythroid burst‐forming unit) progenitors. To test whether the observed alterations involve the release of soluble factors by the epidermal component of skin tumors, we used an in vitro approach. A series of mouse keratinocyte cell lines resembling progressive stages of skin carcinogenesis and carrying either normal or activated Ha‐ ras genes were assayed for their ability to produce the factors required for colony growth of hematopoietic‐committed progenitors. Only the conditioned media of keratinocytes harboring activated Ha‐ ras genes were able to support the growth of granulocyte‐macrophage colony‐forming units. In addition, preincubation of normal bone‐marrow cells with conditioned media from the transformed epidermal cell lines stimulated in vitro amplification of the hematopoietic granulocyte‐macrophage progenitor compartment. To identify the possible factors responsible for the activities detected in the keratinocyte‐conditioned media, we performed northern blot analysis using the cytokine probes granulocyte colony‐stimulating factor, macrophage colony‐stimulating factor, granulocyte‐macrophage colony‐stimulating factor, stem cell factor, interleukin‐1α, interleukin‐3, and tumor necrosis factor‐α. The cell lines expressed different cytokine mRNA combinations that positively correlated with the colony‐stimulating activity detected in the corresponding conditioned medium. These results suggest that transformed epidermal tumor cells in vivo may alter normal hematopoiesis as a consequence of the production of cytokines that act in autocrine or paracrine loops probably related to tumor growth. ©1994 Wiley‐Liss, Inc.